Mammalian cells containing a nucleic acid that encodes a recombinant protein are often used to produce therapeutically or commercially important proteins. In the current environment of diverse product pipelines, biotechnology companies are increasingly driven to develop innovative solutions for highly flexible and cost-effective manufacturing of therapeutic agents.
Mammalian cells containing a nucleic acid that encodes a recombinant protein are often cultured in large production bioreactors to produce therapeutic proteins of interest. Seed train processes are used to generate a sufficient number of such mammalian cells to inoculate the large production bioreactors. Conventional seed train processes start with the thawing of a cryopreserved cell bank vial, followed by multiple culturing steps (e.g., 5 or more) in progressively larger culture vessels. Conventional seed train processes have several disadvantages including the requirement for multiple manual manipulations during each step, which makes the whole process vulnerable to contamination and operator error. In addition, conventional seed train processes are time-consuming due to the number of culturing steps, and due to the low cell densities achieved at the N−1 step (cell culture penultimate to the inoculation of the production bioreactor) that can only result in a starting cell density of less than 0.5×106 cells/mL in large-scale production bioreactors, which requires a 5-10 day growth phase in order to reach the steady state production cell density.